Respiratory Syncytial Virus (RSV) in Older Adults: A Hidden Annual Epidemic Wednesday, November 2, 2016 12:00 PM ET Webinar Agenda Agenda Welcome and Introductions William Schaffner, MD, NFID Medical Director Personal and Societal Burden of RSV: Clinical Presentation, Diagnosis, Current and Future Prevention & Treatment Strategies Edward E. Walsh, MD, University of Rochester Medical Center Questions & Answers This webinar is supported by an unrestricted educational grant from Novavax, Inc. NFID policies restrict funders from controlling program content. 1
Disclosures Marla Dalton (NFID staff) owns stock, stock options, or bonds from Merck & Co., Inc. William Schaffner (NFID medical director, presenter) served as an advisor or consultant for Dynavax, Merck & Co., Inc., Novavax, Inc., Pfizer Inc. and Sanofi Pasteur; and served as a speaker for Genentech Edward E. Walsh (presenter) has received research support from Gilead Inc. All other activity planners/reviewers and staff for this activity have no relevant financial relationships to disclose Learning Objectives At the conclusion of this webinar, participants will be able to: Describe the epidemiology of RSV Discuss the clinical presentation and outcome of RSV infection in older adults Explain RSV diagnostic challenges Summarize RSV treatment and prevention strategies 2
About NFID Non profit 501(c)(3) organization dedicated to educating the public and healthcare professionals about causes, treatment, and prevention of infectious diseases across the lifespan Reaches consumers, health professionals, and media through: Coalition building activities Public and professional educational program Scientific meetings, research, and training Longstanding partnerships to facilitate rapid program initiation and increase programming impact Flexible and nimble organization NFID Resources www.nfid.org/rsv 3
Personal and Societal Burden of RSV: Clinical Presentation, Diagnosis, Current and Future Prevention & Treatment Strategies Edward E. Walsh, MD Professor of Medicine University of Rochester School of Medicine Rochester, NY RSV is a pneumovirus in the Paramyxovirus family Similar to Parainfluenza and measles viruses An ss enveloped RNA virus with 10 genes First discovered in 1956, RSV is best known for causing annual winter time epidemics of bronchiolitis in infants Also linked to asthma 4
Epidemiology and Impact of RSV in Elderly Adults 4 winter seasons 1999 2003 Prospective surveillance of healthy elderly, adults with cardiopulmonary disease Adults hospitalized with acute cardiopulmonary conditions Diagnosis of influenza and RSV by culture, one tube nested RT PCR, serology Falsey et al. NEJM. 2005;352:1749. 5
Rates of Illness and Infection by Cohort, 1999 2003 Group Enrolled Illnesses Healthy Old 622 535 High Risk 528 502 Hospitalized 1481 1569 Falsey et al. NEJM. 2005;352:1749. Incidence of Influenza A and RSV in Older Adults 1999 2000 2000 2001 2001 2002 2002 2003 N=420 N=553 N=375 N=467 Flu A 2.4 0.2 4.3 1.5 RSV 7.6 6.9 3.2 4.1 RSV: 5.5 per 100 / season (3.2 7.6) Flu A: 2.1 per 100 / season (0.2 4.3) 10% of infections were asymptomatic Falsey et al. NEJM. 2005;352:1749. 6
Percent Admissions Due to RSV and Flu A % Admissions 20 15 10 5 0 18 6 12 0.6 17 9 9 3 Flu A RSV Average RSV 10.5 % Flu A 11.6 % 1999-00 2000-01 2001-02 2002-03 Falsey et al. NEJM. 2005;352:1749. Admitting Diagnosis RSV Influenza A Pneumonia 7% 6% 7% COPD CHF Asthma Bronchitis 13% 39% 8% 9% 46% MI Other 35% 23% Falsey et al. NEJM. 2005;352:1749. 7
Functional Impact in Healthy Elderly % 80 70 60 50 40 30 20 10 0 67 54 39 30 25 7 Housebound Bedbound Unable to do ADLs RSV Flu A Falsey et al. NEJM. 2005;352:1749. Outcome of Hospitalized Subjects % 35 30 25 20 15 10 5 0 30 30 13 15 13 11 8 7 Pneumonia ICU Ventilator Death Flu RSV Falsey et al. NEJM. 2005;352:1749. 8
Risk Factors for Hospitalization with RSV P Risk Factor Odds Ratio value Male sex 2.4.17 Pulmonary disease 4.0.03 Coronary Artery Disease 1.0 NS Congestive heart failure 1.9 NS Diabetes 0.9 NS Functional score (per integer 1 12) 1.7.001 Neutralizing titer <10 log 2 5.9.006 Walsh et al. J Infect Dis. 2004;189:233 8. Risk Factors for Hospitalization with RSV 508 hospitalized adults age 65 years PCR over 3 winters in Nashville, TN Virus Incidence (%) % ICU Mortality RSV 6.1% 10% 6% Influenza 6.5% 13% 9% hmpv 4.5% 6% 0% Widmer et al. JID. 2012;206:56 62. 9
Age Specific Annual Deaths in US: P & I and Circulatory & Respiratory Age (years) All Flu RSV <1 39 335 1 4 91 32 5 49 1061 641 50 64 3084 1816 >65 39977 11199 Total 44252 14028 Thompson et al. JAMA. 2003;289:179 86. Projections of US RSV Burden Using surveillance data from Rochester, NY Hospitalizations: 177,000 Deaths: 14,000 10
FLU Optimal model had a 2 3 week lag for RSV deaths in adults Von Asten et al. JID. 2012;206:628 39. Deaths Attributable During Study Period, 1999 2007 Poisson regression model to estimate mortality from RSV & flu in elderly adults in The Netherlands During 9 years influenza ~1.6 fold > RSV Virus 65 74 years 75 84 years 85 years 65 years Flu A 1,935 6,282 7,201 15,519 RSV 1,305 5,171 7,425 13,902 Flu B 2,209 3,907 6,116 Von Asten et al. JID. 2012;206:628 39. 11
RSV and Flu Incidence and Morbidity in Adults 65+ Based on Modeling Author Location Thompson US Mullooly Oregon, US Zhou US van Asten Netherlands Matias US Fleming UK Chan Hong Kong Goldstein NYC Outcome Measure Results RSV/Flu % Respiratory & circulatory deaths per 100,000 Annual pneumonia & influenza hospitalizations per 10,000 Annual hospitalizations per 100,000 RSV 26.5 Flu A+B 98.5 RSV 23.4 Flu 55.6 RSV 86.1 Flu 309 Total deaths RSV 13,902 Flu A + B 21,635 Annual deaths from respiratory illness Annual hospitalizations (ratio of RSV:Flu) Annual hospitalizations per 10,000 Annual hospitalizations per 100,000 RSV 9,673 Flu 16505 26% 42% 28% 64% 59% RSV 14,039 (0.8:1) 80% RSV 5.2 (M) 6.1 (F)** Flu A 19.5 (M) 17.3 (F) RSV 15.3 Flu 125.8 27 35% 12% Office RSV and Influenza, 1995-1998 % of samples 50 40 30 20 10 0 430 314 949 321 167 <1 5..14 15..44 45..64 >65 Age Group RSV Flu Zambon MC. Lancet. 2001;358:1410 16. 12
New Data from Flu Vaccine Efficacy Studies Using Test Negative Control Groups 1,568 adults age >50 years presenting with medicallyattended respiratory illness, 6 seasons at Marshfield Clinic Virus No. % Influenza 343 21.9 RSV 170 10.8 Rhinovirus 126 8.0 hmpv 125 8.0 Coronavirus 122 7.8 Sundaram et al. CID. 2013; 57:789 93. Symptoms in Outpatients RSV Influenza A Healthy n=48, % High Risk n=54, % Healthy n=18, % High Risk n=16, % Nasal 83 65 83 79 Cough 79 78 83 87 Sputum 64 66 61 80 Dyspnea 9 58 28 71 Wheeze 23 50 17 50 Constitutional 53 59 72 71 Fever 18 31 44 47 Sundaram et al. CID. 2014; 342 9. 13
Clinical Findings of RSV in Comparison to Other Viruses also Affecting Elderly Adults 120 100 80 60 40 20 Flu A RSV HMPV hcov 0 Symptoms of RSV and Flu A in Hospitalized Patients Are Very Similar Favors Flu Abrupt High Fever Myalgia GI Symptoms Favors RSV Gradual Rhinorrhea Wheezing Sputum 14
Marshfield Clinic Data 2014 ARI symptoms RSV+ n (%) RSV n(%) P value Cough 202 (99.0) 1857 (91.9) <.001 Wheezing 135 (66.8) 997 (49.4) <.0001 Nasal congestion 182 (89.7) 1570 (77.7) <.0001 Fever 124 (61.1) 1303 (64.8).29 Fatigue 184 (90.2) 1824 (90.3).98 Headache 134 (65.7) 1403 (69.5).27 Muscle aches 116 (56.9) 1283 (63.7).05 ARI=acute respiratory illness. Sundaram et al. CID. 2014; 342 9. RSV Culture + 15
Diagnosis of RSV in the Elderly Comparison of Standard Methods and RT PCR Sensitivity Antigen BD EIA 9% Antigen VIDAS 23% Antigen DFA 27% Culture 39% PCR 73% Serology 95% 16
Adult RSV Infection 17
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Management O2, fluids, standard supportive care Make a correct and accurate diagnosis WHY Antivirals (small molecules and antibodies) perhaps in the not so distant future Antibacterials????? 19
How Were These Patients Treated? Almost all (92%) received antibiotics but very few had evidence of bacterial infection Virus Infiltrates Bacteremic chest X ray Influenza A 30% <1% RSV 31% 3% hmpv 27% 1% Coronavirus (229E/OC43) 12%/37% 0%/0% What Is the Incidence of Bacterial Co Infection During Viral Infection? Historical data from 1918 influenza pandemic: 95% of deaths due to bacterial pneumonia 1957 1958 influenza pandemic estimates of 40 50% of deaths were bacterial 2009 H1N1 pandemic suggesting severe fatal pneumonia was often bacterial Descriptions of bacterial pneumonia during RSV, parainfluenza virus & metapneumovirus infections in adults 20
Bacterial Complications of RT Viral Illness in Rochester, NY 842 hospitalizations during 3 winter seasons 348 viral infection (41%) 212 virus alone (61%)* 64 bacteria specific dx + 72 elevated serum PCT 0.25 ng/ml *74% by RT PCR. Falsey et al. J Infect Dis. 2013;208:432 41. Virus (N) Bacteriaspecific dx PCT 0.25 ng/ml Bacteriaspecific or PCT 0.25 ng/ml Influenza A (83) 10 28 33 (40%) Influenza B (7) 1 3 3 (43%) RSV (55) 10 14 17 (31%) hmpv (38) 10 9 15 (39%) HCoV OC43 (56) 8 19 22 (39%) HCoV 229E (16) 3 6 7 (44%) PIV 1 3 (24) 7 9 12 (50%) Rhinovirus (30) 5 6 9 (30%) Mixed viral (38) 10 10 18 (47%) TOTAL (348) 64 105 136 (39%) Falsey et al. J Infect Dis. 2013;208:432 41. 21
Vaccines Antivirals Diagnostics Antibiotic Reduction Serum Neutralizing Titers and Illness Severity Hospitalized vs Non-Hospitalized No. of Subjects 18 16 14 12 10 8 6 4 2 0 <8.0 8.01-9.00 9.01-10.0 10.01-11.0 MNA 11.01-12.0 12.01-13.0 13.01-18.0 Hospitalized Non- Hospitalized Walsh et al. J Infect Dis. 2004: 189:233 8. 22
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